Are coagulation profiles in Andean highlanders with excessive erythrocytosis favouring hypercoagulability?
blood coagulation
chronic mountain sickness
excessive erythrocytosis
hypoxia
thromboelastometry
Journal
Experimental physiology
ISSN: 1469-445X
Titre abrégé: Exp Physiol
Pays: England
ID NLM: 9002940
Informations de publication
Date de publication:
30 Mar 2024
30 Mar 2024
Historique:
received:
14
11
2023
accepted:
18
03
2024
medline:
30
3
2024
pubmed:
30
3
2024
entrez:
30
3
2024
Statut:
aheadofprint
Résumé
Chronic mountain sickness is a maladaptive syndrome that affects individuals living permanently at high altitude and is characterized primarily by excessive erythrocytosis (EE). Recent results concerning the impact of EE in Andean highlanders on clotting and the possible promotion of hypercoagulability, which can lead to thrombosis, were contradictory. We assessed the coagulation profiles of Andeans highlanders with and without excessive erythrocytosis (EE+ and EE-). Blood samples were collected from 30 EE+ and 15 EE- in La Rinconada (Peru, 5100-5300 m a.s.l.), with special attention given to the sampling pre-analytical variables. Rotational thromboelastometry tests were performed at both native and normalized (40%) haematocrit using autologous platelet-poor plasma. Thrombin generation, dosages of clotting factors and inhibitors were measured in plasma samples. Data were compared between groups and with measurements performed at native haematocrit in 10 lowlanders (LL) at sea level. At native haematocrit, in all rotational thromboelastometry assays, EE+ exhibited hypocoagulable profiles (prolonged clotting time and weaker clot strength) compared with EE- and LL (all P < 0.01). At normalized haematocrit, clotting times were normalized in most individuals. Conversely, maximal clot firmness was normalized only in FIBTEM and not in EXTEM/INTEM assays, suggesting abnormal platelet activity. Thrombin generation, levels of plasma clotting factors and inhibitors, and standard coagulation assays were mostly normal in all groups. No highlanders reported a history of venous thromboembolism based on the dedicated survey. Collectively, these results indicate that EE+ do not present a hypercoagulable profile potentially favouring thrombosis.
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Grenoble Alpes University Fundation
Organisme : Agence Nationale de la Recherche (ANR)
ID : ANR-15-IDEX-02
Organisme : Agence Nationale de la Recherche (ANR)
ID : ANR-12-TECS-0010
Organisme : Air Liquid Foundation
Organisme : Fonds de dotation AGIR pour les maladies chroniques
Informations de copyright
© 2024 The Authors. Experimental Physiology published by John Wiley & Sons Ltd on behalf of The Physiological Society.
Références
Azad, P., Stobdan, T., Zhou, D., Hartley, I., Akbari, A., Bafna, V., & Haddad, G. G. (2017). High‐altitude adaptation in humans: From genomics to integrative physiology. Journal of Molecular Medicine, 95, 1269–1282.
Beall, C. M (2007). Two routes to functional adaptation: Tibetan and Andean high‐altitude natives. Proceedings of the National Academy of Sciences, 104, (suppl_1), 8655–8660.
Bontekoe, I. J., van der Meer, P. F., & Korte, D. (2019). Thromboelastography as a tool to evaluate blood of healthy volunteers and blood component quality: A review. Vox Sanguinis, 114(7), 643–657.
Champigneulle, B., Brugniaux, J. V., Stauffer, E., Doutreleau, S., Furian, M., Perger, E., Pina, A., Baillieul, S., Deschamps, B., Hancco, I., Connes, P., Robach, P., Pichon, A., & Verges, S. (2023). Expedition 5300: Limits of human adaptations in the highest city in the world. The Journal of Physiology, Advance online publication. https://doi.org/10.1113/jp284550
Champigneulle, B., Hancco, I., Hamard, E., Doutreleau, S., Furian, M., Brugniaux, J. V., Bailly, S., & Vergès, S. (2022). Excessive erythrocytosis and chronic mountain sickness in the highest city in the world: A longitudinal study. Chest, 161(5), 1338–1342.
DeSouza, N. M., Brewster, L. M., Bain, A. R., Garcia, V. P., Stone, R., Stockelman, K. A., Greiner, J. J., Tymko, M. M., Vizcardo‐Galindo, G., Figueroa‐Mujica, R. J., Villafuerte, F. C., Ainslie, P. N., & DeSouza, C. A. (2021). Global REACH 2018: Influence of excessive erythrocytosis on coagulation and fibrinolytic factors in Andean highlanders. Experimental Physiology, 106(6), 1335–1342..
Frezzato, M., Tosetto, A., & Rodeghiero, F. (1996). Validated questionnaire for the identification of previous personal or familial venous thromboembolism. American Journal of Epidemiology, 143(12), 1257–1265.
Gangaraju, R., Song, J., Kim, S. J., Tashi, T., Reeves, B. N., Sundar, K. M., Thiagarajan, P., & Prchal, J. T. (2020). Thrombotic, inflammatory, and HIF‐regulated genes and thrombosis risk in polycythemia vera and essential thrombocythemia. Blood Advances, 4(6), 1115–1130.
Gordeuk, V. R., Key, N. S., & Prchal, J. T. (2019). Re‐evaluation of hematocrit as a determinant of thrombotic risk in erythrocytosis. Haematologica, 104(4), 653–658.
Gordeuk, V. R., Miasnikova, G. Y., Sergueeva, A. I., Lorenzo, F. R., Zhang, X., Song, J., Stockton, D. W., & Prchal, J. T. (2020). Thrombotic risk in congenital erythrocytosis due to up‐regulated hypoxia sensing is not associated with elevated hematocrit. Haematologica, 105(3), e87–e90.
Görlinger, K., Dirkmann, D., Solomon, C., & Hanke, A. A. (2013). Fast interpretation of thromboelastometry in non‐cardiac surgery: Reliability in patients with hypo‐, normo‐, and hypercoagulability. British Journal of Anaesthesia, 110(2), 222–230.
Hancco, I., Bailly, S., Baillieul, S., Doutreleau, S., Germain, M., Pépin, J.‐L., & Verges, S. (2020). Excessive erythrocytosis and chronic mountain sickness in dwellers of the highest city in the world. Frontiers in Physiology, 11, 773.
Hancco, I., Champigneulle, B., Stauffer, E., Pichon, A., Robach, P., Brugniaux, J. V., Savina, Y., Doutreleau, S., Connes, P., & Vergès, S. (2020). Hemostasis in highlanders with excessive erythrocytosis at 5100 m: Preliminary data from the highest city of the world. Respiratory Physiology & Neurobiology, 282, 103535.
Jiang, P., Wang, Z., Yu, X., Qin, Y., Shen, Y., Yang, C., Liu, F., Ye, S., Du, X., Ma, L., Cao, H., Sun, P., Su, N., Lin, F., Zhang, R., & Li, C. (2021). Effects of long‐term high‐altitude exposure on fibrinolytic system. Hematology (Amsterdam, Netherlands), 26(1), 503–509.
Kitchen, S., Adcock, D. M., Dauer, R., Kristoffersen, A., Lippi, G., Mackie, I., Marlar, R. A., & Nair, S. (2021). International Council for Standardisation in Haematology (ICSH) recommendations for collection of blood samples for coagulation testing. International Journal of Laboratory Hematology, 43(4), 571–580.
Kroll, M. H., Michaelis, L. C., & Verstovsek, S. (2015). Mechanisms of thrombogenesis in polycythemia vera. Blood Reviews, 29(4), 215–221.
Lang, T., Bauters, A., Braun, S. L., Pötzsch, B., von, P. K.‐W., Kolde, H.‐J., & Lakner, M. (2005). Multi‐centre investigation on reference ranges for ROTEM thromboelastometry. Blood Coagulation & Fibrinolysis, 16(4), 301–310.
Lang, T., Johanning, K., Metzler, H., Piepenbrock, S., Solomon, C., Rahe‐Meyer, N., & Tanaka, K. A. (2009). The effects of fibrinogen levels on thromboelastometric variables in the presence of thrombocytopenia. Anesthesia Analgesia, 108(3), 751–758.
León‐Velarde, F., Maggiorini, M., Reeves, J. T., Aldashev, A., Asmus, I., Bernardi, L., Ge, R.‐L., Hackett, P., Kobayashi, T., Moore, L. G., Penaloza, D., Richalet, J.‐P., Roach, R., Wu, T., Vargas, E., Zubieta‐Castillo, G., & Zubieta‐Calleja, G. (2005). Consensus statement on chronic and subacute high altitude diseases. High Altitude Medicine & Biology, 6(2), 147–157.
Lill, M. C., Perloff, J. K., & Child, J. S. (2006). Pathogenesis of thrombocytopenia in cyanotic congenital heart disease. American Journal of Cardiology, 98(2), 254–258.
Lordkipanidzé, M. (2016). Platelet function tests. Seminars in Thrombosis and Hemostasis, 42(3), 258–267.
Luddington, R. J. (2005). Thrombelastography/thromboelastometry. Clinical & Laboratory Haematology, 27(2), 81–90.
Mairbäurl, H., Gassmann, M., & Muckenthaler, M. U. (2020). Geographical ancestry affects normal hemoglobin values in high‐altitude residents. Journal of Applied Physiology, 129(6), 1451–1459.
Marlar, R. A., Potts, R. M., & Marlar, A. A. (2006). Effect on routine and special coagulation testing values of citrate anticoagulant adjustment in patients with high hematocrit values. American Journal of Clinical Pathology, 126(3), 400–405.
Martin, D. S., Pate, J. S., Vercueil, A., Doyle, P. W., Mythen, M. G., Grocott, M. P. W., & Group, C. (2017). Reduced coagulation at high altitude identified by thromboelastography. Thrombosis and Haemostasis, 107(6), 1066–1071.
Maslow, A., Cheves, T., Joyce, M. F., Apruzzese, P., & Sweeney, J. (2023). Interaction between platelet and fibrinogen on clot strength in healthy patients. Journal of Cardiothoracic and Vascular Anesthesia, 37(6), 942–947.
Moore, L. G. (2017). Measuring high‐altitude adaptation. Journal of Applied Physiology, 123(5), 1371–1385.
Nagler, M., Kathriner, S., Bachmann, L. M., & Wuillemin, W. A. (2013). Impact of changes in haematocrit level and platelet count on thromboelastometry parameters. Thrombosis Research, 131(3), 249–253.
Nguyen, E., Harnois, M., Busque, L., Sirhan, S., Assouline, S., Chamaki, I., Olney, H., Mollica, L., & Szuber, N. (2021). Phenotypical differences and thrombosis rates in secondary erythrocytosis versus polycythemia vera. Blood Cancer Journal, 11(4), 75.
Noorman, F., & Hess, J. R. (2018). The contribution of the individual blood elements to the variability of thromboelastographic measures. Transfusion, 58(10), 2430–2436.
Oberholzer, L., Lundby, C., Stauffer, E., Ulliel‐Roche, M., Hancco, I., Pichon, A., Lundby, A.‐K. M., Villafuerte, F. C., Verges, S., & Robach, P. (2020). Reevaluation of excessive erythrocytosis in diagnosing chronic mountain sickness in men from the world's highest city. Blood, 136(16), 1884–1888.
Ortiz‐Prado, E., Cordovez, S. P., Vasconez, E., Viscor, G., & Roderick, P. (2022). Chronic high‐altitude exposure and the epidemiology of ischaemic stroke: A systematic review. BMJ Open, 12(4), e051777.
Pamenter, M. E., Hall, J. E., Tanabe, Y., & Simonson, T. S. (2020). Cross‐species insights into genomic adaptations to hypoxia. Frontiers Genetics, 11, 743.
Pujol, C., Stöckl, A., Mebus, S., Röschenthaler, F., Holdenrieder, S., Ewert, P., Nagdyman, N., Neidenbach, R. C., & Kaemmerer, H. (2019). Value of rotational thromboelastometry and impedance aggregometry for evaluating coagulation disorders in patients with cyanotic and nongenetic congenital heart disease. American Journal of Cardiology, 123(10), 1696–1702.
Racine‐Brzostek, S. E., & Asmis, L. M. (2020). Assessment of platelet function utilizing viscoelastic testing. Transfusion, 60(S6), S10–S20.
Rocke, A. S., Paterson, G. G., Barber, M. T., Jackson, A. I. R., Main, S. E., Stannett, C., Schnopp, M. F., MacInnis, M., Baillie, J. K., Horn, E. H., Moores, C., Harrison, P., Nimmo, A. F., & Thompson, A. A. R. (2018). Thromboelastometry and platelet function during acclimatization to high altitude. Thrombosis and Haemostasis, 118(1), 063–071.
Rupa‐Matysek, J., Trojnarska, O., Gil, L., Szczepaniak‐Chicheł, L., Wojtasińska, E., Tykarski, A., Grajek, S., & Komarnicki, M. (2016). Assessment of coagulation profile by thromboelastometry in adult patients with cyanotic congenital heart disease. International Journal of Cardiology, 202, 556–560.
Şahin, D. G., Akay, O. M., Teke, H. U., Andıc, N., & Gunduz, E. (2021). Use of rotational thromboelastometry for a global screening of coagulation profile in patients of myeloproliferative neoplasms. Platelets, 32(2), 280–283.
Small, M., Lowe, G. D. O., Cameron, E., & Forbes, C. D. (1983). Contribution of the haematocrit to the bleeding time. Pathophysiology of Haemostasis and Thrombosis, 13(6), 379–384.
Solomon, C., Rahe‐Meyer, N., Schöchl, H., Ranucci, M., & Görlinger, K. (2012). Effect of haematocrit on fibrin‐based clot firmness in the FIBTEM test. Blood transfusion, 11, 412–418.
Solomon, C., Ranucci, M., Hochleitner, G., Schöchl, H., & Schlimp, C. J. (2015). Assessing the methodology for calculating platelet contribution to clot strength (platelet component) in thromboelastometry and thrombelastography. Anesthesia Analgesia, 121(4), 868–878.
Stauffer, E., Loyrion, E., Hancco, I., Waltz, X., Ulliel‐Roche, M., Oberholzer, L., Robach, P., Pichon, A., Brugniaux, J. V., Bouzat, P., Doutreleau, S., Connes, P., & Verges, S. (2020). Blood viscosity and its determinants in the highest city in the world. The Journal of Physiology, 598(18), 4121–4130.
Tremblay, J. C., & Ainslie, P. N. (2021). Global and country‐level estimates of human population at high altitude. Proceedings of the National Academy of Sciences, 118(18), e2102463118.
Treml, B., Wallner, B., Blank, C., Fries, D., & Schobersberger, W. (2022). The influence of environmental hypoxia on hemostasis—A systematic review. Frontiers Cardiovasc Medicine, 9, 813550.
Tripodi, A. (2020). Thrombin generation: A global coagulation procedure to investigate hypo‐ and hyper‐coagulability. Haematologica, 105(9), 2196–2199.
Tripodi, A., Chantarangkul, V., Gianniello, F., Clerici, M., Lemma, L., Padovan, L., Gatti, L., Mannucci, P. M., & Peyvandi, F. (2013). Global coagulation in myeloproliferative neoplasms. Annal of Hematology, 92(12), 1633–1639.
Villafuerte, F. C., & Corante, N. (2016). Chronic Mountain Sickness: Clinical Aspects, Etiology, Management, and Treatment. High Altitude Medicine & Biology, 17(2), 61–69.
Villafuerte, F. C., Simonson, T. S., Bermudez, D., & León‐Velarde, F. (2022). High‐altitude erythrocytosis: Mechanisms of adaptive and maladaptive responses. Physiology, 37(4), 175–186.
Volod, O., Bunch, C. M., Zackariya, N., Moore, E. E., Moore, H. B., Kwaan, H. C., Neal, M. D., Al‐Fadhl, M. D., Patel, S. S., Wiarda, G., Al‐Fadhl, H. D., McCoy, M. L., Thomas, A. V., Thomas, S. G., Gillespie, L., Khan, R. Z., Zamlut, M., Kamphues, P., Fries, D., & Walsh, M. M. (2022). Viscoelastic hemostatic assays: A primer on legacy and new generation devices. Journal of Clinical Medicine, 11(3), 860.
Wang, Y., Huang, X., Yang, W., & Zeng, Q. (2022). Platelets and high‐altitude exposure: A meta‐analysis. High Altitude Medicine & Biology, 23(1), 43–56.
Wang, Z., Tenzing, N., Xu, Q., Liu, H., Ye, Y., Wen, Y., Wuren, T., & Cui, S. (2023). Apoptosis is one cause of thrombocytopenia in patients with high‐altitude polycythemia. Platelets, 34(1), 2157381.
Weisel, J. W., & Litvinov, R. I. (2019). Red blood cells: The forgotten player in hemostasis and thrombosis. Journal of Thrombosis and Haemostasis, 17(2), 271–282.
Westbury, S. K., Lee, K., Reilly‐Stitt, C., Tulloh, R., & Mumford, A. D. (2013). High haematocrit in cyanotic congenital heart disease affects how fibrinogen activity is determined by rotational thromboelastometry. Thrombosis Research, 132(2), e145–e151.
Yin, Y., Geng, H., Cui, S., & Hua‐Ji, L. (2022). Correlation of platelet‐derived growth factor and thromboxane A2 expression with platelet parameters and coagulation indices in chronic altitude sickness patients. Experimental Physiology, 107(8), 807–812.
Zangari, M., Fink, L., Tolomelli, G., Lee, J. C. H., Stein, B. L., Hickman, K., Swierczek, S., Kelley, T. W., Berno, T., Moliterno, A. R., Spivak, J. L., Gordeuk, V. R., & Prchal, J. T. (2013). Could hypoxia increase the prevalence of thrombotic complications in polycythemia vera? Blood Coagulation and Fibrinolysis, 24(3), 311–316.